Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 7, 2011; 17(9): 1219-1226
Published online Mar 7, 2011. doi: 10.3748/wjg.v17.i9.1219
Metastasis-associated protein 1 induces VEGF-C and facilitates lymphangiogenesis in colorectal cancer
Bin Du, Zhen-Yu Yang, Xue-Yun Zhong, Mao Fang, Yong-Rong Yan, Guo-Long Qi, Yun-Long Pan, Xu-Long Zhou
Bin Du, Zhen-Yu Yang, Xue-Yun Zhong, Mao Fang, Yong-Rong Yan, Xu-Long Zhou, Department of Pathology, Medical School of Jinan University, Guangzhou 510632, Guangdong Province, China
Guo-Long Qi, Division of Medical Informatics, Medical School of Jinan University, Guangzhou 510632, Guangdong Province, China
Yun-Long Pan, Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou 510632, Guangdong Province, China
Author contributions: Du B and Yang ZY contributed equally to this work; Du B and Zhou XL designed the research and wrote the manuscript; Yang ZY, Fang M and Yan YR performed the experiments; Du B and Qi GL performed the statistical analysis; Zhong XY offered the new reagents and helpful comments on the manuscript; Pan YL collected the clinical data and provided some useful comments during the study; all authors approved the final manuscript.
Supported by National Natural Science Foundation of China (No. 30772131) and Fundamental Research Funds for Central Universities (No. 21609313) from Ministry of Education of China
Correspondence to: Xu-Long Zhou, Associate Professor, Department of Pathology, Medical School of Jinan University, Guangzhou 510632, Guangdong Province, China. tzhouxl@hotmail.com
Telephone: +86-20-85220252 Fax: +86-20-85221343
Received: November 1, 2010
Revised: December 9, 2010
Accepted: December 16, 2010
Published online: March 7, 2011
Abstract

AIM: To study the correlation between high metastasis-associated protein 1 (MTA1) expression and lymphangiogenesis in colorectal cancer (CRC) and its role in production of vascular endothelial growth factor-C(VEGF-C).

METHODS: Impact of high MTA1 and VEGF-C expression levels on disease progression and lymphovascular density (LVD, D2-40-immunolabeled) in 81 cases of human CRC was evaluated by immunohistochemistry. VEGF-C mRNA and protein expressions in human LoVo and HCT116 cell lines were detected by real-time polymerase chain reaction and Western blotting, respectively, with a stable expression vector or siRNA.

RESULTS: The elevated MTA1 and VEGF-C expression levels were correlated with lymph node metastasis and Dukes stages (P < 0.05). Additionally, high MTA1 expression level was correlated with a large tumor size (P < 0.05). A significant correlation was found between MTA1 and VEGF-C protein expressions in tumor cells (r = 0.371, P < 0.05). Similar to the VEGF-C expression level, high MTA1 expression level was correlated with high LVD in CRC (P < 0.05). Furthermore, over-expression of MTA1 significantly enhanced the VEGF-C mRNA and protein expression levels, whereas siRNAs - knocked down MTA1 decreased the VEGF-C expression level.

CONCLUSION: MTA1, as a regulator of tumor-associated lymphangiogenesis, promotes lymphangiogenesis in CRC by mediating the VEGF-C expression.

Keywords: Metastasis-associated protein 1; Vascular endothelial growth factor-C; Lymphangiogenesis; Colorectal cancer